Anal Sphincters

Researchers at the Wake Forest Institute for Regenerative Medicine have built the first functional anal sphincters in the
laboratory, suggesting a potential future treatment for both fecal and urinary incontinence. Made from muscle and nerve
cells, the sphincters developed a blood supply and maintained function when implanted in mice.

Sphincters are ring-like muscles that maintain constriction of a body passage. There are numerous sphincters in the human
body, including those that control the release of urine and feces. There are actually two sphincters at the anus, one
internal and one external. Fecal incontinence is the result of a weakened internal sphincter.

There is a high incidence of weakened internal fecal sphincters in older adults. Women who have had episiotomies during childbirth
can also be affected. Unfortunately, many individuals attempt to hide the problem from their families, friends and even
their doctors and suffer without help.

Current options for repair of the internal anal sphincter include grafts of skeletal muscle, injectable silicone material
or implantation of mechanical devices, all of which have high complication rates and limited success.

Research Significance

The research team has built a replacement sphincter that they hope can one day benefit human patients. This is the first
bioengineered sphincter made with both muscle and nerve cells, making it “pre-wired” for placement in the
body.

Research Approach and Goals

To engineer an internal anal sphincter in the laboratory, the researchers used a small biopsy from a human sphincter and
isolated smooth muscle cells that were then multiplied in the lab. In a ring-shaped mold, these cells were layered with
nerve cells isolated from mice to build the sphincter. The mold was placed in an incubator for nine days, allowing for
tissue formation. The entire process took about six weeks.

Numerous laboratory tests of the engineered sphincters, including stimulating the nerve cells, showed normal tissue function,
such as the ability to relax and contract. The sphincters were then implanted just under the skin of mice to determine
how they would respond in the body. Mice with suppressed immune systems were selected so that there would be no issues
with rejection.

After 25 days of implantation, each sphincter was re-tested and also compared with the animals’ native sphincters.
The engineered sphincters had developed a blood vessel supply and continued to function like native tissue.

Research Highlights and Innovation

The research takes the team one step closer to being able to use a patient’s own cells to engineer a replacement sphincter
in the lab.

Research Update: Engineering Intestinal Tissue in the Lab

Khalil Bitar, PhD, professor at Wake Forest Institute for Regenerative Medicine overviews his current research and explains engineering intestinal tissue in the lab.

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